Oral squamous cell cancer (OSCC) is the sixth most common cancer worldwide and accounts for 2% of all malignancies in the USA. In this year alone, 40,000 men and women will develop OSCC, and unfortunately, only two-thirds of these OSCC patients will survive more than five years. While the past decades have seen advances in ablative/reconstructive surgery, radiation therapy, and chemotherapy, the overall survival rate of OSCC patients has not improved significantly, and there are multiple co-morbidities which arise from treatment which may negatively affect quality of life. Thus, there is a real need for innovative new approaches to treating oral squamous cell cancer. Cancer immunotherapy has arisen as a novel treatment modality for several cancers, and an implantable, polymeric cancer vaccine has been developed by the Mooney laboratory which shows impressive tumor killing in both melanoma and glioma preclinical models. Our goal is to evaluate this promising cancer vaccine technology for use in oral squamous cell carcinoma. Our overall hypothesis is that an in situ cancer vaccine construct able to provide appropriate spatiotemporal presentation of bioactive factors to host dendritic cells can induce anti-tumor immunity. The studies outlined in this proposal seek to determine the effectiveness of the implantable cancer vaccine for treating OSCC, to optimize the various components of the cancer vaccine for maximum potency, and to explore any synergistic effects which arise by combining this vaccine with other immunotherapeutic tools such as tumor-specific monoclonal antibodies. Overall, these studies are anticipated to enhance our understanding of the role dendritic cells and tumor-specific cytotoxic T cells play in the treatment of OSCC, and may also contribute to the development of novel immunotherapies for OSCC.